CLDN18 (Claudin 18)

P2/3, N=126, Not yet recruiting, AstraZeneca AB

P1/2, N=45, Not yet recruiting, Gilead Sciences Inc.

It highlights several cutting-edge directions, including the discovery of novel targets (e.g., Claudin 18.2, B7-H3), innovative CAR designs (e.g., logic-gated CARs, armored CARs), local delivery and in situ generation techniques, and combination therapies (e.g., with radiotherapy, immune checkpoint inhibitors, oncolytic viruses). Finally, this review outlines future directions of developing intelligent, controllable next-generation CAR-T technologies through multidisciplinary integration, hoping to provide a valuable perspective for advancing basic research and clinical translation in this field.

P1/2, N=26, Not yet recruiting, Gilead Sciences Inc.

Digital image analysis, radiomics, and machine learning are likely to improve quantification and may support future biomarker integration. A practical pathology-oriented approach should prioritize tissue stewardship, conservative interpretation of IHC results, and close coordination with molecular methods.

Finally, we critically assess translational barriers, including organ-specific metastatic tropism and resistance evolution, and propose that the convergence of deep molecular profiling, neural-immune modulation, and AI-enabled computational oncology will be central to advancing precision medicine for GC. This integrated framework aims to accelerate the development of mechanism-based combination therapies.

P1/2, N=42, Recruiting, Beijing Biotech

The patient was treated with combination chemotherapy and immune checkpoint inhibition. This case highlights an atypical presentation of advanced gastroesophageal junction adenocarcinoma in a young adult and underscores the importance of early endoscopic evaluation in patients with persistent dysphagia, as well as recognition of uncommon metastatic patterns and the therapeutic implications of biomarker profiling.

P2, N=389, Recruiting, Innovent Biologics (Suzhou) Co. Ltd. | Not yet recruiting --> Recruiting

P1/2, N=36, Recruiting, Beijing Biotech

Background: Claudin 18.2 (CLDN18.2) has become a clinically relevant therapeutic target in gastric adenocarcinoma (GC), with zolbetuximab now approved for use in CLDN18.2-positive, HER2-negative advanced disease... CLDN18.2 shows excellent intratumoral reproducibility and a stable biological profile in GC, supporting its diagnostic reliability in biopsies and value as a predictive biomarker. A subset with extreme expression demonstrated aggressive features, suggesting a potential "claudin-driven" phenotype requiring further study.

To confirm encouraging first clinical data, larger studies specific for BTC are needed to address tumor heterogeneity and to determine cutoff levels of CLDN-18.2 expression. Such studies are also needed to understand combination options and sequencing of therapies and to further validate novel approaches to fully exploit the potential of targeting CLDN-18.2 in BTC.